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Changes of tight junctions induced by extracellular stimuli determine cell shape and fate.

Research Project

Project/Area Number 16K08693
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

SAWADA NORIMASA  札幌医科大学, 医学部, 教授 (30154149)

Co-Investigator(Kenkyū-buntansha) 村田 雅樹  札幌医科大学, 医学部, 講師 (10404592)
Research Collaborator TAKASAWA KUMI  
AKIMOTO TAISHI  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsタイト結合 / JAM-A / claudin / occludin / tricellulin / claudin-18 / シグナル伝達 / 造腫瘍性 / フェンス機能 / 細胞ストレス / 上皮細胞接着 / “タイト結合病”
Outline of Final Research Achievements

The tight junction (TJ) is an intercellular junction that works as a barrier to external stimulation and as a fence to maintain cell polarity. Recently, aberrant expression of TJ proteins have been reported in various diseases. In this study, we focused mainly on aberrant expression in human tumor and clarified the following. TJ proteins could be diagnostic markers for some tumors including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, lung adenocarcinoma, cervical adenocarcinoma and salivary gland tumors. These findings suggested that TJ proteins are promising targets of cancer therapy. Furthermore, the expression of TJ proteins were involved in the enhancement of the malignancy of carcinoma such as invasion and proliferation. These findings suggested that abnormality of TJ might be involved in tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

ヒト癌における細胞間接着装置タイト結合の構成分子の役割を検討し、膵癌ではtricellulin、肺癌ではJAM-A、胆管癌ではclaudin-18が、癌の進行に関与していること、子宮頚部腺癌ではclaudin-1が予後不良因子でGRP30を介してエストロゲン依存性に発現していることを明らかにした。これらは、各タイト結合分子が診断マーカー又は治療標的分子となりうることを意味し、急増する種々の癌に対する新しい治療戦略を提案するもので、社会的影響や意義は大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(17 results)

All 2019 2018 2017 2016

All Journal Article

  • [Journal Article] Immunoreactivity patterns of tight junction proteins are useful for differential diagnosis of human salivary gland tumors.2019

    • Author(s)
      Aoyama T, Takasawa A, Murata M, Osanai M, Takano K, Hasegawa T, Sawada N
    • Journal Title

      Med Mol Morphol.

      Volume: 52 Pages: 23-35

    • DOI

      10.1007/s00795-018-0199-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Coiled-Coil Domain-Containing Protein 180 and Leucine-Rich Repeat-Containing Protein 4 as Potential Immunohistochemical Markers for Liposarcoma Based on Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded Tissue.2019

    • Author(s)
      Aoyama T, Takasawa A, Takasawa K, Ono Y, Emori M, Murata M, Hayasaka T, Fujitani N, Osanai M, Yamashita T, Hasegawa T, Sawada N.
    • Journal Title

      Am J Pathol

      Volume: in press

    • DOI

      10.1016/j.ajpath.2019.01.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retinoic acid-metabolizing enzyme cytochrome P450 26A1 promotes skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.2018

    • Author(s)
      Osanai M, Takasawa A, Takasawa K, Murata M, Sawada N
    • Journal Title

      Oncol Lett.

      Volume: 15 Pages: 9987-9993

    • DOI

      10.3892/ol.2018.8599

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytotoxicity of Clostridium perfringens enterotoxin depends on the conditions of claudin-4 in ovarian carcinoma cells.2018

    • Author(s)
      Tanaka S, Aoyama T, Ogawa M, Takasawa A, Murata M, Osanai M, Saito T, Sawada N
    • Journal Title

      Experimental Cell Research

      Volume: 371 Pages: 278-286

    • DOI

      10.1016/j.yexcr.2018.08.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression.2018

    • Author(s)
      Akimoto T, Takasawa A, Takasawa K, Aoyama T, Murata M, Osanai M, Saito T, Sawada N
    • Journal Title

      Neoplasia

      Volume: 10 Pages: 1083-1093

    • DOI

      10.1016/j.neo.2018.08.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Occludin induces microvillus formation via phosphorylation of ezrin in a mouse hepatic cell line2018

    • Author(s)
      Ueda A, Takasawa A, Akimoto T, Takasawa K, Aoyama T, Ino Y, Nojima M, Ono Y, Murata M, Osanai M, Hasegawa T, Saito T, Sawada N.
    • Journal Title

      Exp Cell Res.

      Volume: 12(8) Pages: 172-180

    • DOI

      10.1016/j.yexcr.2018.03.018

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Claudins in cancer: bench to bedside.2017

    • Author(s)
      Makoto Osanai, Akira Takasawa, Masaki Murata, Norimasa Sawada
    • Journal Title

      Pflugers Arch Eur J Physiol.

      Volume: - Pages: 55-67

    • DOI

      10.1007/s00424-016-1877-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Surfactant protein A (SP-A) and SP-A-derived peptide attenuate chemotaxis of mast cells induced by human β-defensin 32017

    • Author(s)
      Uehara Y., Takahashi M., Murata M., Saito A., Takamiya R., Hasegawa Y., Kuronuma K., Chiba H., Hashimoto J., Sawada N., Takahashi H., Kuroki Y., Ariki S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 485 Pages: 107-112

    • DOI

      10.1016/j.bbrc.2017.02.028

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surfactant Protein A Inhibits Growth and Adherence of UropathogenicEscherichia coliTo Protect the Bladder from Infection2017

    • Author(s)
      Hashimoto J., Takahashi M., Satio A., Murata M., Kurimura Y., Nishitani C., Takamiya R., Uehara Y., Hasegawa Y., Hiyama Y., Sawada N., Takahashi S., Masumori N., Kuroki Y., Ariki S.
    • Journal Title

      Journal of immunology

      Volume: 198 Pages: 2898-2905

    • DOI

      10.4049/jimmunol.1502626

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytological findings of langerhans cell sarcoma in a case of quintuple cancer.2017

    • Author(s)
      Tabata S, Murata M, Takasawa A, Fukuda A, Ogasawara J, Koseki T, Nakano K, Segawa K, Morita R, Hasegawa T, Sawada N.
    • Journal Title

      Diagn Cytopathol.

      Volume: 45(5) Pages: 441-445

    • DOI

      10.1002/dc.23628

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Caludin-18 coupled with EGFR/ERK signaling contributes to the malignant potentials of bile duct cancer2017

    • Author(s)
      Takasawa K, Takasawa A, Osanai M, Aoyama T, Ono Y, Kono T, Hirohashi Y, Murata M, Sawada N.
    • Journal Title

      Cancer Lett

      Volume: 403 Pages: 66-73

    • DOI

      10.1016/j.canlet.2017.05.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma2017

    • Author(s)
      Magara K, Takasawa A, Osanai M, Ota M, Tagami Y, Ono Y, Takasawa K, Murata M, Hirohashi Y, Miyajima M, Yamada G, Hasegawa T, Sawada N.
    • Journal Title

      Cancer Science

      Volume: 108(11) Pages: 2306-2314

    • DOI

      10.1111/cas.13385

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1, -4, -7, occludin and JAM-A, in human cervical adenocarcinoma.2016

    • Author(s)
      Akimoto T, Takasawa A, Murata M, Kojima Y, Takasawa K, Nojima M, Aoyama T, Hiratsuka Y, Ono Y, Tanaka S, Osanai M,Hasegawa T, Saito T, Sawada N.
    • Journal Title

      Histol Histopathol

      Volume: 31(8) Pages: 921-931

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expressions of claudin 4 and 7in atypical adenomatous hyperplasia and adenocarcinoma of the lung.2016

    • Author(s)
      Yamada G, Murata M, Takasawa A, Nojima M, Mori Y, Sawada N, Takahashi H.
    • Journal Title

      Med Mol Morphol

      Volume: 49(3) Pages: 163-169

    • DOI

      10.1007/s00795-016-0135-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Claudins-4 and -7 might be valuable markers to distinguish hepatocellular carcinoma from cholangiocarcinoma.2016

    • Author(s)
      Yusuke Ono, Yutaro Hiratsuka, Masaki Murata, Akira Takasawa, Rieko Fukuda, Masanori Nojima, Satoshi Tanaka, Makoto Osanai, Koichi Hirata, Norimasa Sawada
    • Journal Title

      Virchows Arch

      Volume: 469 Pages: 417-426

    • DOI

      10.1007/s00428-016-1984-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Claudins in cancer: bench to bedside.2016

    • Author(s)
      Osanai M, Takasawa A, Murata M, Sawada N.
    • Journal Title

      Pflugers Ach

      Volume: 469(1) Pages: 55-67

    • DOI

      10.3892/or.2016.5072

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nuclear localization of tricellulin promotes the oncogenic property of pancreatic cancer.2016

    • Author(s)
      Takasawa A, Murata M, Takasawa K, Ono Y, Osanai M, Tanaka S, Nojima M, Kono T, Hirata K, Kojima T, Sawada N.
    • Journal Title

      Sci Rep

      Volume: 19(6) Pages: 33582-33582

    • DOI

      10.1038/srep33852

    • Related Report
      2016 Research-status Report
    • Peer Reviewed

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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